Abstract for IMM20003

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.

Indium phosphate is a material used as a semiconductor in the electronics industry as is gallium arsenide. The primary interest in these studies relates to the immunotoxicological studies of GaAs. GaAs was shown to have a selective action on the immune system and arsenic was implicated as the immunotoxicological component. As a semiconductor material, there is also an interest to evaluate IP for an immunotoxicological component.

Indium phosphate was nominated to the NTP for toxicological evaluation and was selected f or immunotoxicity studies by the chemical manager. Thus, the purpose of this range-finding study was to determine the doses of IP to be used in the protocol to determine the potential effects of IP on the immune system.

The range-finding studies were conducted in female B6C3F1 mice. The animals were administered IP on day one by a single intratracheal instillation. IP was prepared as a solution in sterile physiological saline with 0.05% Tween 80. The animals were exposed for varying time periods after the single intratracheal instillation, including days 3, 4, 5, 6, 8, 9, 12, 14, and 17. The T-dependent antibody response to sheep erythrocytes was measured at all exposure time periods. The body weight data were obtained at all time periods. The mixed leukocyte response, hematology, organ weight and body weight were assessed after nine days of exposure.

The results of indium phosphate range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure between 50 and 200 mg/kg by a single intratracheal instillation produces a consistent decrease in body weight at the 200 mg/kg dose at most of the time periods evaluated. The decrease compared to the control group ranges from 11 to 29%. The liver weight was significantly decreased at the 150, and 200 mg/kg doses by 24 and 22%, respectively, after nine days of exposure. The lung weight was significantly increased in all doses by 44 to 91% as compared to the vehicle control lung weight. In the hematology parameters, the reticulocytes were significantly decreased at doses of 100, 150, and 200 mg/kg with percent changes of 34, 62, and 68%, respectively.

A summary of the immunology studies demonstrated that exposure to indium phosphate for nine days did not affect the mixed leukocyte response. The results from several time course studies demonstrated that the antibody-forming cell response to the T-dependent antigen sheep erythrocytes was significantly decreased after an exposure period of 3, 5, 12, and 14 days at 200 mg/kg, and, after an exposure period of 11, 13, 15, and 17 days, a decrease dose-related trend was seen. A significant decrease in spleen cell number was seen throughout the studies at 200 mg/kg.